The Induction of Immunologic Memory after Vaccination with<i>Haemophilus influenzae</i>Type b Conjugate and Acellular Pertussis–Containing Diphtheria, Tetanus, and Pertussis Vaccine Combination

296

194

The antibody data supporting the use of meningococcal serogroup C conjugate (MCC) vaccines in the United Kingdom were generated by serum bactericidal assay (SBA) using rabbit complement (rSBA). This may give higher titers than those obtained with human complement (hSBA), for which the "gold standard" correlate of protection for meningococcal C disease is a titer of >4. Comparison of rSBA and hSBA titers in sera from unvaccinated adults with an rSBA titer of >8 showed that for 93% (27 of 29) the titer was >4 by hSBA, confirming natural protection. Furthermore, sera from MCC vaccinees showed that an rSBA titer of <8 or >128 discriminated susceptibility and protection well (85% with rSBA titers of <8 had hSBA titers of <4, and 99% with rSBA titers of >128 had hSBA titers of >4). However, discrimination was poor in the rSBA titer range 8 to 64, with only 60% having hSBA titers of >4. In such cases we propose that protection can be assumed if there is a fourfold rise in titer between pre-and postvaccination sera or if there is a characteristic booster response to a polysaccharide challenge dose with, if available, evidence of antibody avidity maturation or an hSBA titer of result >4. Applying these criteria to toddlers, 10 to 40% of whom had titers in the range 8 to 64 after a single dose of MCC vaccine, showed that 94% had a fourfold rise in titer, including 98% of those in the titer range 8 to 64. In addition, of those with titers of <128 post-MCC vaccination, 90% had titers of >128 after a 10-g polysaccharide booster dose, compared with only 7% of unprimed age-matched toddlers given a full 50-g dose. Furthermore, the increase in geometric mean avidity index pre-and postbooster was independent of post-primary MCC titer. These results indicated that the majority of toddlers with an rSBA titer between 8 and 64, and some of those with an hSBA result of <4, have mounted a protective immune response with the induction of immunological memory.

Section: Discussionmentioning

confidence: 99%

Serological Basis for Use of Meningococcal Serogroup C Conjugate Vaccines in the United Kingdom: Reevaluation of Correlates of Protection

Borrow

Andrews²,

Miller³

2001

296

194

“…The fact that the quantity of antigen used for the primary series is positively correlated with postprimary rSBA levels but negatively correlated with the magnitude of the booster response is important since both anticap-sular antibody and immunologic memory play a role in immunity to N. meningitidis, as is also true for Hib (12). The recent observations of a resurgence of Hib disease and a decline in efficacy in the United Kingdom (17) among a population of children immunized with a three-dose vaccine course known reliably to indue immune memory (10) suggest that absolute levels of circulating antibody may be of more importance than previously thought.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity of, and Immunologic Memory to, a Reduced Primary Schedule of Meningococcal C-Tetanus Toxoid Conjugate Vaccine in Infants in the United Kingdom

Borrow

Green

Finn³

et al. 2003

It has been previously shown that one of the three meningococcal C conjugate (MCC) vaccines introduced in the United Kingdom proved highly immunogenic after the first dose of a three-dose schedule, with evidence of immune memory after dose 3. Thus, in infants a one-or two-dose schedule of this MCC vaccine, conjugated to tetanus toxoid (TT), may suffice. Healthy infants (n ‫؍‬ 586) were randomized to receive either one (group 1), two (group 2), or three (group 3) doses of MCC-TT vaccine with a 10-g polysaccharide booster given at 13 to 14 months of age. Serum bactericidal antibody (SBA) levels were measured by utilizing rabbit complement (rSBA), meningococcal C-specific immunoglobulin G (IgG), and avidity indices (AIs). For groups 1, 2, and 3, the percentages of infants with an rSBA level of >8 against strain C11 were 98.4, 100, and 99.4%, respectively. Infants in group 1 with prevaccination rSBA titers of >8 had post-primary MCC rSBA geometric mean titers (GMTs) significantly lower than those infants with prevaccination rSBA titers of <8. One dose of MCC-TT vaccine given to infants at 2 months of age yielded significantly lower SBA GMTs and geometric mean AIs (GMAIs) than two or three doses but elicited a significantly greater response after boosting, as reflected by rSBA levels and GMAI. This study provides the first evidence that the number of doses of MCC-TT used in infant immunization schedules could be decreased.In November 1999, the United Kingdom introduced universal meningococcal C conjugate (MCC) vaccination at 2, 3, and 4 months of age, on the basis of safety and immunogenicity studies (15). A prelicensure study in 83 infants in the United Kingdom (18) who were given one of the three candidate MCC vaccines, a tetanus toxoid conjugate (MCC-TT) (14), at 2, 3, and 4 months of age demonstrated that the vaccine was highly immunogenic after a single dose at 2 months of age, with all infants achieving a putative protective antibody titer of Ն8 (bactericidal antibody levels in serum were measured with baby rabbit complement [rSBA]) (1a, 3). There was a further significant increase in antibody levels after a second dose of MCC-TT vaccine but no further increase after the third dose at 4 months of age. Antibody levels fell by 14 months of age, but booster antibody responses to meningococcal C polysaccharide and MCC vaccines provided evidence of successful priming for immunologic memory after the full course of three doses (18).The excellent response to this MCC-TT vaccine among infants at 2 months of age and the modest response to the third dose of vaccine raise the possibility that a one-or two-dose schedule in infants may be sufficient to provide protection from meningococcal C disease. Demonstration of priming for immune memory by the one-or two-dose schedules suggests that these regims could also provide long-term protection. This could be assessed by examining antibody responses to meningococcal C polysaccharide vaccination in the second year of life since children do not normally respond to polysaccharide ...

“…In contrast to subsequently described ELISA methods that use chaotropic agents to dissociate antigen-antibody complexes (2,17,18) and give estimates of avidity (avidity index), the RABA method (Fig. 2) allows direct calculation of a Ka.…”

Section: Discussionmentioning

confidence: 99%

Age-Related Disparity in Functional Activities of Human Group C Serum Anticapsular Antibodies Elicited by Meningococcal Polysaccharide Vaccine

Harris¹,

King

Ferris

et al. 2003

Serum bactericidal activity confers protection against meningococcal disease, but it is not known whether vaccine-induced anticapsular antibodies that lack bactericidal activity are protective. We developed an infant rat challenge model using a naturally occurring O-acetylated strain of Neisseria meningitidis group C and a strain that was negative for O acetylation (OAc). Rats 4 to 7 days of age inoculated intraperitoneally (i.p.) with ϳ10 3 CFU of either strain developed >5 ؋ 10 5 CFU/ml of blood obtained 18 h later. Dilutions of preimmunization sera given i.p. 2 h before the bacterial challenge had no effect on bacteremia, whereas group C anticapsular antibody in sera from adults immunized with meningococcal polysaccharide vaccine conferred complete or partial (>99% decrease in CFU per milliliter of blood) protection against the OAc-positive or OAc-negative strain, respectively, at antibody doses as low as 0.04 g/rat. Anticapsular antibody at doses fivefold higher (0.18 to 0.2 g/rat) in pooled sera from children immunized at a mean age of 2.6 years failed to protect rats, but antibody at the same or fivefold-lower dose in a serum pool from a group of children immunized at 4 years of age gave complete or partial protection. Protective activity was observed with some serum pools that lacked detectable complement-mediated bactericidal activity (titers < 1:4) and correlated with increasing antibody avidity. Thus, not only does the magnitude of the group C antibody response to meningococcal polysaccharide vaccine increase with increasing age but there are also age-related affects on antibody functional activity such that higher serum concentrations of vaccine-induced antibody are required for protection of immunized children than for immunized adults.